Lipid-conjugates are thought to inhibit the enzyme phospholipase A2 (PLA2, EC 3.1.1.4). Phospholipase A2 catalyzes the breakdown of phospholipids at the sn-2 position to produce a fatty acid and a lysophospholipid. The activity of this enzyme has been correlated with various cell functions, particularly with the production of lipid mediators such as eicosanoid production (prostaglandins, thromboxanes and leukotrienes), platelet activating factor and lysophospholipids. Lipid-conjugates may offer a wider scope of protection of cells and organisms from injurious agents and pathogenic processes, including the prevention and treatment of microbial infections.
Microbial infections (e.g., infections by viral or bacterial species) account for significant morbidity and mortality throughout the world. Although significant resources have been dedicated to identifying compounds having antimicrobial properties, microbial infections continue to present a significant human health risk.
There are relatively few effective pharmaceutical compositions intended or adapted for antiviral, antifungal, or antiparasitic therapy. A major obstacle in the development of antiviral agents is the difficulty in distinguishing viral replicative mechanisms from host replicative processes. An additional limitation of existing antiviral drugs is that they have a narrow antiviral spectrum and are often ineffective against the latent virus.
There are a much larger number of existing antibacterial agents, which has led to a significant decrease in morbidity and mortality from infectious diseases in this century. This important public health contribution has been largely due to the widespread use of antibiotics that target specific nutrient, cell wall, DNA, RNA and protein biosynthetic pathways that are particular to pathogenic bacteria. However, in recent years the capacity to manage infectious diseases has been threatened by the emergence of bacterial strains that are no longer susceptible to currently available antimicrobial agents. The widespread use of available antibacterial agents has led to the development of increasing numbers of antibiotic resistant bacteria.
In fact, the usefulness of most existing antimicrobial treatments are limited by the development of multidrug resistance and the emergence of long-term toxicities. Other challenges include creating a drug that is broadly applicable in combating many different types of microbial infections, which is especially important in the treatment of immunocompromised individuals.